title: Quinacrine and 9-amino acridine inhibit B-Z and B-H(l) form DNA conformational transitions.
abstract: The interaction of quinacrine and 9-amino acridine with right-handed B-form, left-handed Z-form, and left-handed protonated (H(L))-form structures of polydG-me(5)dC was investigated by circular dichroism and absorption spectral analysis. Both the compounds bind strongly to the B-form structure and convert the Z-form and H(L)-form back to the bound right-handed form. Circular dichroic data revealed that the conformation at the binding site is right-handed even though adjacent regions of the polynucleotide may have left-handed conformation. The rate and extent of B-form-to-Z-form transition were decreased in the presence of these compounds. Scatchard analysis revealed that both quinacrine and 9-amino acridine bind strongly to the polynucleotide in the B-form in a noncooperative manner, in sharp contrast to the highly cooperative binding to the Z-form and H(L)-form. Results indicated that the cooperative binding of these drugs with the Z-form and the H(L)-forms was associated with a sequential conversion of the polynucleotide from a left-handed to a bound right-handed conformation. Experimental data enabled the calculation of the number of base pairs of Z-form (7-8 with quinacrine and 9-amino acridine) and H(L)-form (4 and 25, respectively, with quinacrine and 9-amino acridine) that adopt a right-handed conformation for each bound ligand. As these compounds are known to bind preferentially to alternating guanine--cytosine sequences, which are capable of easily undergoing the B-to-Z or B-to-H(L) transition, these effects may be important in understanding their biological activities.
authors.affiliation: Department of Chemistry, Jadavpur University, Kolkata, India. sumandas10@yahoo.com
authors.forename: Suman
authors.initials: S
authors.lastname: Das
authors.forename: Suprabhat
authors.initials: S
authors.lastname: Kundu
authors.forename: Gopinatha
authors.initials: G
authors.lastname: Suresh Kumar
mesh_terms: D000585:Aminacrine / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D043542:DNA, Z-Form / Q000737:chemistry*; D007700:Kinetics; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D011796:Quinacrine / Q000737:chemistry*
chemical_list: D043542:DNA, Z-Form; D000585:Aminacrine; D004247:DNA; D011796:Quinacrine